Chemical Pathology 3 - Acid Base handling

Question 1

What are the 3 main buffering systems in the body?

Answer 1

bicarbonate is the main one

Question 2

How is pH control achieved in the proximal convuluted tubule?

Answer 2

1. H+ and HCO3- combine in tubule lumen to form H2CO3
2. Carbonic anhydrase on tubule tumen membrane converts H2CO3 to H2O and CO2 and absorbs it into the tubule wall cell
3. H2O + CO2 –> H2CO3 again inside the cell, via carbonic anhydrase II
4. Bicarbonate is exchanged with chloride ions, releasing into the capillary
5. H+ ions can be actively secreted into the tubule lumen, or transported via a sodium-proton exchanger

Question 3

Recall 3 broad mechanisms of aetiology of metabolic acidosis

Answer 3

1. H+ prodution (eg DKA)
2. Decreased H+ excretion (eg renal tubular acidosis)
3. Bicarbonate loss (eg intestinal fistula)

Question 4

Describe the change in the acid-base equilibrium in a metabolic acidosis

Answer 4

Equilibrium =
HCO3- + H+ H2CO3 H2O + CO2
Extra H+ produced by acidosis pushes reaction RIGHT
CO2 production increases –> blown out by increased ventilation

Question 5

Describe the change in the acid-base equilibrium in a respiratory acidosis

a) acutely
b) chronically

Answer 5

Equilibrium =
HCO3- + H+ H2CO3 H2O + CO2

a) acutely:

Excess CO2 produced by reduced ventilation pushes reaction LEFT, so more H+ and HCO3- is produced (this is PRIOR TO COMPENSATION)

b) Chronically:

CO2 remains raised (due to reduced ventilation), and HCO3- remains raised to maintain physiological pH - so in chronic COPD etc you would see elevated bicarbonate

Question 6

Describe the change in the acid-base equilibrium in a metabolic alkalosis

Answer 6

Equilibrium =
HCO3- + H+ H2CO3 H2O + CO2

Pathology = decreased H+ / increased HCO3-

• loss of H+ (pyloric stenosis)
• increased ingestion of bicarbonate (antacids)

- hypokalaemia (hypkalaemia and alkalosis go together)

Either way - need to regenerate H+
Therefore, EQUILIBRIUM moves LEFT
To do this: resp rate decreases (to increase CO2)

Question 7

What are the possible causes of metabolic alkalosis?

Answer 7

H+ loss: pyloric stenosis, hypokalaemia

HCO3- excess: lots of Rennies

Question 8

Describe the acute change in the acid-base equilibrium in a respiratory alkalosis

Answer 8

Equilibrium =
HCO3- + H+ H2CO3 H2O + CO2
Hyperventilation –> reduced CO2
Reaction moves RIGHT to restore CO2

Question 9

Describe the chronic change in the acid-base equilibrium in a respiratory alkalosis

Answer 9

Equilibrium =
HCO3- + H+ H2CO3 H2O + CO2

Acutely, reaction moves RIGHT to restore CO2 (so you get low H+ and HCO3-)

Chronically, kidneys compensate by reducing H+ excretion - so H+ returns to normal, but HCO3- and CO2 remain low

Question 10

When can you get a mixed respiratory and metabolic acidosis?

Answer 10

eg COPD patient with diabetes mellitus

COPD- respiratory acidosis

Diabetes mellitus- metabolic acidosis

Question 11

Normal pH

Answer 11

7.35 – 7.45

Question 12

Normal CO2

Answer 12

4.7 – 6kPa

Question 13

Normal bicarb

Answer 13

22 – 30 mmol/l

Question 14

Normal O2

Answer 14

10 – 13kPa

Question 15

Biochemical abnormlaities and causes of metabolic acidosis

Answer 15

pH: low

pCO2: low

Hco3: low

Causes

1) High AG: KULT

Ketones

Uraemia

Lactic acid

Toxins- ethylene glycol, metformin (biguanide), methanol, paraaldehyde, salicylate

2) Normal anion gap

Diarrhoea (small bowel GI loss of HCO3), Acetazolamide (CA inhibitor), high output stoma, pancreatic fistula (loss of bicarb), Addison’s, renal tubular acidosis, ammonium chloride ingestion

Question 16

Metabolic alkalosis

Answer 16

pH: high

CO2: high (due to the hypoventilation)

Bicarb: high

causes

Vomiting (H+ loss)(bulimia), Loop diuretics (K+ depletion), hypokalaemia, Conn’s (hyperaldosteronism, (immediate)
K+ loss), antacid use, burns

Question 17

Respiratory acidosis

Answer 17

pH: low

CO2: high

bicarb: high

causes

Hypoventilation (T2 resp failure): Acute/chronic lung disease (commonest = COPD), opioids, sedatives, neuromuscular weakness

Normal/high PaCO2 worrying - ITU RV/vent support (exhaustion)

Question 18

Respiratory alkalosis

Answer 18

pH: high

co2: low
bicarb: low

Causes:

Hyperventilation: Stroke; SAH, meningitis, asthma, alkalosis
anxiety, PE, pregnancy, altitude (hypoxaemia),
↓renal [HCO3-]
salicylates (early – brainstem stimulation)

Question 19

Calculation of anion gap

Answer 19

(Na+ + K+) – (Cl- + HCO3)

Question 20

Osmolality (measured) – Osmolarity (calculated)

Answer 20

Normal osmolar gap = < 10 • An elevated osmolar gap provides indirect evidence for the presence of an abnormal solute • The osmolar gap is increased by extra solutes in the plasma (e.g. alcohols, mannitol, ketones,
lactate) • Can be raised in advanced CKD due to retained small solutes • Helpful in differentiating the cause of an elevated anion gap metabolic acidosis

Question 21

What is the key equation that explains buffering?

Answer 21

H+ excreted by kidneys

CO2 excreted by lungs

Question 22

What abnormality of acid base do you get in aspirin overdose?

Answer 22

Mixed respiratory alkalosis and metabolic acidosis

Why?

a) Aspirin stimulates respiratory centre–>respiratory alkalosis
b) Aspirin inhibits bicarbonate reabsorption in kidney –>metabolic alkalosis

Question 23

Mnemonic for remembering causes of raised anion gap

Answer 23

MUDPILES

Metformin/methanol

Uraemia

DKA

Paraldehyde

Iron

Lactate

EThanol

Salicylcates